Preferential Inhibition of Tonically over Phasically Activated NMDA Receptors by Pregnane Derivatives
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F16%3A10388127" target="_blank" >RIV/00216208:11320/16:10388127 - isvavai.cz</a>
Alternative codes found
RIV/67985823:_____/16:00459355 RIV/61388963:_____/16:00459355
Result on the web
<a href="https://doi.org/10.1523/JNEUROSCI.3181-15.2016" target="_blank" >https://doi.org/10.1523/JNEUROSCI.3181-15.2016</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1523/JNEUROSCI.3181-15.2016" target="_blank" >10.1523/JNEUROSCI.3181-15.2016</a>
Alternative languages
Result language
angličtina
Original language name
Preferential Inhibition of Tonically over Phasically Activated NMDA Receptors by Pregnane Derivatives
Original language description
Postsynaptic N-methyl-D-aspartate receptors (NMDARs) phasically activated by presynaptically released glutamate are critical for synaptic transmission and plasticity. However, under pathological conditions, excessive activation of NMDARs by tonically increased ambient glutamate contributes to excitotoxicity associated with various acute and chronic neurological disorders. Here, using heterologously expressed GluN1/GluN2A and GluN1/GluN2B receptors and rat autaptic hippocampal microisland cultures, we show that pregnanolone sulfate inhibits NMDAR currents induced by a prolonged glutamate application with a higher potency than the NMDAR component of EPSCs. For synthetic pregnanolone derivatives substituted with a carboxylic acid moiety at the end of an aliphatic chain of varying length and attached to the steroid skeleton at C3, the difference in potency between tonic and phasic inhibition increased with the length of the residue. The steroid with the longest substituent, pregnanolone hemipimelate, had no effect on phasically activated receptors while inhibiting tonically activated receptors. In behavioral tests, pregnanolone hemipimelate showed neuroprotective activity without psychomimetic symptoms. These results provide insight into the influence of steroids on neuronal function and stress their potential use in the development of novel therapeutics with neuroprotective action.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Neuroscience
ISSN
0270-6474
e-ISSN
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Volume of the periodical
36
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
2161-2175
UT code for WoS article
000370818700009
EID of the result in the Scopus database
2-s2.0-84958817737